International Journal of Arrhythmia (Jan 2023)

Nonlinear analysis of beat-to-beat variability of action potential time series data identifies dynamic re-entrant substrates in a hypokalaemic mouse model of acquired long QT syndrome

  • Gary Tse,
  • Jiandong Zhou,
  • Xiuming Dong,
  • Guoliang Hao,
  • Sharen Lee,
  • Keith Sai Kit Leung,
  • Fung Ping Leung,
  • Tong Liu,
  • Yimei Du,
  • Shuk Han Cheng,
  • Wing Tak Wong

DOI
https://doi.org/10.1186/s42444-023-00084-4
Journal volume & issue
Vol. 24, no. 1
pp. 1 – 11

Abstract

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Abstract Background Previous studies have quantified repolarization variability using time-domain, frequency-domain and nonlinear analysis in mouse hearts. Here, we investigated the relationship between these parameters and ventricular arrhythmogenicity in a hypokalaemia model of acquired long QT syndrome. Methods Left ventricular monophasic action potentials (MAPs) were recorded during right ventricular regular 8 Hz pacing during normokalaemia (5.2 mM [K+]), hypokalaemia modeling LQTS (3 mM [K+]) or hypokalaemia with 0.1 mM heptanol in Langendorff-perfused mouse hearts. Results During normokalaemia, mean APD was 33.5 ± 3.7 ms. Standard deviation (SD) of APDs was 0.63 ± 0.33 ms, coefficient of variation was 1.9 ± 1.0% and the root mean square (RMS) of successive differences in APDs was 0.3 ± 0.1 ms. Low- and high-frequency peaks were 0.6 ± 0.5 and 2.3 ± 0.7 Hz, respectively, with percentage powers of 38 ± 22 and 61 ± 23%. Poincaré plots of APD n+1 against APD n revealed ellipsoid morphologies with SD along the line-of-identity (SD2) to SD perpendicular to the line-of-identity (SD1) ratio of 4.6 ± 1.1. Approximate and sample entropy were 0.49 ± 0.12 and 0.64 ± 0.29, respectively. Detrended fluctuation analysis revealed short- and long-term fluctuation slopes of 1.62 ± 0.27 and 0.60 ± 0.18, respectively. Hypokalaemia provoked ventricular tachycardia in six of seven hearts, prolonged APDs (51.2 ± 7.9 ms), decreased SD2/SD1 ratio (3.1 ± 1.0), increased approximate and sample entropy (0.68 ± 0.08 and 1.02 ± 0.33) and decreased short-term fluctuation slope (1.23 ± 0.20) (ANOVA, P < 0.05). Heptanol prevented VT in all hearts studied without further altering the above repolarization parameters observed during hypokalaemia. Conclusion Reduced SD2/SD1, increased entropy and decreased short-term fluctuation slope may reflect arrhythmic risk in hypokalaemia. Heptanol exerts anti-arrhythmic effects without affecting repolarization variability.

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